Estudo conformacional e espectroscópico do dipiridamol : uma visão semiempírica
Autor(a) principal: | |
---|---|
Data de Publicação: | 2010 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFS |
Texto Completo: | https://ri.ufs.br/handle/riufs/6066 |
Resumo: | Dipyridamole, 2,6 - bis(diethanolamine) - 4,8- dipiperidinedinapyrimide - [5,4-d] pyrimidine (DIP) is a clinically approved drug for use in cardiology, belonging to the class of heterocyclics with interesting antioxidant properties. In this work we studied the relative stability and properties of six conformational structures of DIP and also aimed to understand the effect of the different conformations on some molecular properties such as the ionization potential. In this study, we used semiempirical methods such as AM1, PM3, PM6 and RM1, all available in the MOPAC2009 program. The solvent effect on the relative stabilities of conformations as well as on the properties of the drug was evaluated using the continuum medium approximation and a sequential Monte Carlo procedure and quantum mechanics (MC/QM). The MC procedure has been used in order to yield liquid configurations, allowing the calculation of average values of solution properties which indicated the possibility of hydrogen bonding involving DIP nitrogen atoms. All calculations performed both in vacuum and in implicit solvent suggest the occurrence of a mixture of possible conformations since the energy difference between them is low. The preferential protonation occurs in nitrogens atoms of the heteroaromatic ring but this preference changes with conformation. In general the greater stabilizations occur when the protons bind to N2 and N7 atoms, in agreement with the calculation considering the solvent. The spectroscopic analysis in water has shown that all three DIP bands exhibit a slight solvatochromism and that only the first solvent layer contributes to those shifts. The charge distribution and the ionization potential under the water effect as solvent were carried out for the 125 structures derived from the MC procedure using PM3 and AM1 methods. It has been found that the distribution of Mulliken charges in PM3 points out that the electron leaves the nitrogen atom more effectively, independently of in aromatic or aliphatic position, while the distribution according to AM1 suggests that the electron preferentially leaves the N2 and N7 atoms, according to the HOMO molecular orbital. |
id |
UFS-2_7273d503ed137f922d01da3de2929df3 |
---|---|
oai_identifier_str |
oai:ufs.br:riufs/6066 |
network_acronym_str |
UFS-2 |
network_name_str |
Repositório Institucional da UFS |
repository_id_str |
|
spelling |
Santos, LucianoCosta Júnior, Nivan Bezerra dahttp://lattes.cnpq.br/64931974835156522017-09-27T13:57:29Z2017-09-27T13:57:29Z2010-08-02SANTOS, Luciano. Estudo conformacional e espectroscópico do dipiridamol : uma visão semiempírica. 2010. 86 f. Dissertação (Mestrado em Química) - Universidade Federal de Sergipe, São Cristóvão, 2010.https://ri.ufs.br/handle/riufs/6066Dipyridamole, 2,6 - bis(diethanolamine) - 4,8- dipiperidinedinapyrimide - [5,4-d] pyrimidine (DIP) is a clinically approved drug for use in cardiology, belonging to the class of heterocyclics with interesting antioxidant properties. In this work we studied the relative stability and properties of six conformational structures of DIP and also aimed to understand the effect of the different conformations on some molecular properties such as the ionization potential. In this study, we used semiempirical methods such as AM1, PM3, PM6 and RM1, all available in the MOPAC2009 program. The solvent effect on the relative stabilities of conformations as well as on the properties of the drug was evaluated using the continuum medium approximation and a sequential Monte Carlo procedure and quantum mechanics (MC/QM). The MC procedure has been used in order to yield liquid configurations, allowing the calculation of average values of solution properties which indicated the possibility of hydrogen bonding involving DIP nitrogen atoms. All calculations performed both in vacuum and in implicit solvent suggest the occurrence of a mixture of possible conformations since the energy difference between them is low. The preferential protonation occurs in nitrogens atoms of the heteroaromatic ring but this preference changes with conformation. In general the greater stabilizations occur when the protons bind to N2 and N7 atoms, in agreement with the calculation considering the solvent. The spectroscopic analysis in water has shown that all three DIP bands exhibit a slight solvatochromism and that only the first solvent layer contributes to those shifts. The charge distribution and the ionization potential under the water effect as solvent were carried out for the 125 structures derived from the MC procedure using PM3 and AM1 methods. It has been found that the distribution of Mulliken charges in PM3 points out that the electron leaves the nitrogen atom more effectively, independently of in aromatic or aliphatic position, while the distribution according to AM1 suggests that the electron preferentially leaves the N2 and N7 atoms, according to the HOMO molecular orbital.O dipiridamol, 2,6-bis(dietanolamina)-4,8-dipiperidinadinapirimida-[5,4-d] pirimidina (DIP), é utilizado como fármaco clinicamente aprovado para utilização na cardiologia, pertencendo a classe de heterocíclicos que apresentam atividades interessantes tais como antioxidante. Neste trabalho, estudou-se estabilidade relativa entre seis estruturas conformacionais do DIP e buscou-se entender como afetam algumas de suas propriedades, como por exemplo, potencial de ionização. Neste estudo utilizamos os métodos semiempíricos AM1, PM3, PM6 e RM1 disponíveis no programa MOPAC2009, procurou-se, também, verificar o efeito do solvente sobre a estabilidade relativa e as propriedades do DIP, para isso usou-se a aproximação do meio contínuo e um procedimento seqüencial de Monte Carlo e mecânica quântica (MC/QM) que gerou as configurações do líquido e propriedades médias em solução foram calculadas e ainda foi verificada a possibilidade de ligações de hidrogênio intermoleculares nos nitrogênios do DIP. Todos os cálculos, sejam no vácuo ou em solvente, sugerem que há uma mistura de conformações, uma vez que a diferença de energia entre elas é pequena. A protonação é preferencial nos nitrogênios do anel aromático, a preferência muda com a conformação, porém a estabilização é, em geral, maior quando o próton liga-se aos N2 e N7. O cálculo com o solvente, também, sugerem que normalmente os N2 e N7 são os nitrogênios mais disponíveis para ligação de hidrogênio. A análise espectroscópica, em água, mostrou que as três bandas do DIP apresentam um pequeno solvatocromismo e que apenas a primeira camada do solvente contribui para os deslocamentos solvatocrômicos. A distribuição de cargas e o calculo do potencial de ionização do DIP, sob efeito do solvente água, foram feitos para as 125 estruturas derivadas do MC usando o PM3 e o AM1, sendo que a distribuição de cargas de Mulliken no PM3 aponta para uma saída mais efetiva do elétron nos nitrogênios quer seja aromático ou não, enquanto que a distribuição AM1 sugerem que o elétron sai preferencialmente dos N2 e N7, conforme o orbital molecular do HOMO.application/pdfporUniversidade Federal de SergipePós-Graduação em QuímicaUFSBRAnálise químicaAnálise espectroscópicaFarmacologiaDipiridamolChemical analysisSpectroscopic analysisPharmacologyDipyridamoleCNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICAEstudo conformacional e espectroscópico do dipiridamol : uma visão semiempíricaCONFORMATIONAL ANALYSIS AND SPECTROSCOPY DIPYRIDAMOLE: a vision semiempirical.info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSinstname:Universidade Federal de Sergipe (UFS)instacron:UFSORIGINALLUCIANO_SANTOS.pdfapplication/pdf1827869https://ri.ufs.br/jspui/bitstream/riufs/6066/1/LUCIANO_SANTOS.pdfcdab31def522c05f4ddbb4089d8e7bfeMD51TEXTLUCIANO_SANTOS.pdf.txtLUCIANO_SANTOS.pdf.txtExtracted texttext/plain116928https://ri.ufs.br/jspui/bitstream/riufs/6066/2/LUCIANO_SANTOS.pdf.txted40475697ae3430e20648bda90ab702MD52THUMBNAILLUCIANO_SANTOS.pdf.jpgLUCIANO_SANTOS.pdf.jpgGenerated Thumbnailimage/jpeg1275https://ri.ufs.br/jspui/bitstream/riufs/6066/3/LUCIANO_SANTOS.pdf.jpgdea554ae1291fce46c9c3f38bd2868e2MD53riufs/60662018-01-16 19:40:42.772oai:ufs.br:riufs/6066Repositório InstitucionalPUBhttps://ri.ufs.br/oai/requestrepositorio@academico.ufs.bropendoar:2018-01-16T22:40:42Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS)false |
dc.title.por.fl_str_mv |
Estudo conformacional e espectroscópico do dipiridamol : uma visão semiempírica |
dc.title.alternative.eng.fl_str_mv |
CONFORMATIONAL ANALYSIS AND SPECTROSCOPY DIPYRIDAMOLE: a vision semiempirical. |
title |
Estudo conformacional e espectroscópico do dipiridamol : uma visão semiempírica |
spellingShingle |
Estudo conformacional e espectroscópico do dipiridamol : uma visão semiempírica Santos, Luciano Análise química Análise espectroscópica Farmacologia Dipiridamol Chemical analysis Spectroscopic analysis Pharmacology Dipyridamole CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
title_short |
Estudo conformacional e espectroscópico do dipiridamol : uma visão semiempírica |
title_full |
Estudo conformacional e espectroscópico do dipiridamol : uma visão semiempírica |
title_fullStr |
Estudo conformacional e espectroscópico do dipiridamol : uma visão semiempírica |
title_full_unstemmed |
Estudo conformacional e espectroscópico do dipiridamol : uma visão semiempírica |
title_sort |
Estudo conformacional e espectroscópico do dipiridamol : uma visão semiempírica |
author |
Santos, Luciano |
author_facet |
Santos, Luciano |
author_role |
author |
dc.contributor.author.fl_str_mv |
Santos, Luciano |
dc.contributor.advisor1.fl_str_mv |
Costa Júnior, Nivan Bezerra da |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/6493197483515652 |
contributor_str_mv |
Costa Júnior, Nivan Bezerra da |
dc.subject.por.fl_str_mv |
Análise química Análise espectroscópica Farmacologia Dipiridamol |
topic |
Análise química Análise espectroscópica Farmacologia Dipiridamol Chemical analysis Spectroscopic analysis Pharmacology Dipyridamole CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
dc.subject.eng.fl_str_mv |
Chemical analysis Spectroscopic analysis Pharmacology Dipyridamole |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
description |
Dipyridamole, 2,6 - bis(diethanolamine) - 4,8- dipiperidinedinapyrimide - [5,4-d] pyrimidine (DIP) is a clinically approved drug for use in cardiology, belonging to the class of heterocyclics with interesting antioxidant properties. In this work we studied the relative stability and properties of six conformational structures of DIP and also aimed to understand the effect of the different conformations on some molecular properties such as the ionization potential. In this study, we used semiempirical methods such as AM1, PM3, PM6 and RM1, all available in the MOPAC2009 program. The solvent effect on the relative stabilities of conformations as well as on the properties of the drug was evaluated using the continuum medium approximation and a sequential Monte Carlo procedure and quantum mechanics (MC/QM). The MC procedure has been used in order to yield liquid configurations, allowing the calculation of average values of solution properties which indicated the possibility of hydrogen bonding involving DIP nitrogen atoms. All calculations performed both in vacuum and in implicit solvent suggest the occurrence of a mixture of possible conformations since the energy difference between them is low. The preferential protonation occurs in nitrogens atoms of the heteroaromatic ring but this preference changes with conformation. In general the greater stabilizations occur when the protons bind to N2 and N7 atoms, in agreement with the calculation considering the solvent. The spectroscopic analysis in water has shown that all three DIP bands exhibit a slight solvatochromism and that only the first solvent layer contributes to those shifts. The charge distribution and the ionization potential under the water effect as solvent were carried out for the 125 structures derived from the MC procedure using PM3 and AM1 methods. It has been found that the distribution of Mulliken charges in PM3 points out that the electron leaves the nitrogen atom more effectively, independently of in aromatic or aliphatic position, while the distribution according to AM1 suggests that the electron preferentially leaves the N2 and N7 atoms, according to the HOMO molecular orbital. |
publishDate |
2010 |
dc.date.issued.fl_str_mv |
2010-08-02 |
dc.date.accessioned.fl_str_mv |
2017-09-27T13:57:29Z |
dc.date.available.fl_str_mv |
2017-09-27T13:57:29Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
SANTOS, Luciano. Estudo conformacional e espectroscópico do dipiridamol : uma visão semiempírica. 2010. 86 f. Dissertação (Mestrado em Química) - Universidade Federal de Sergipe, São Cristóvão, 2010. |
dc.identifier.uri.fl_str_mv |
https://ri.ufs.br/handle/riufs/6066 |
identifier_str_mv |
SANTOS, Luciano. Estudo conformacional e espectroscópico do dipiridamol : uma visão semiempírica. 2010. 86 f. Dissertação (Mestrado em Química) - Universidade Federal de Sergipe, São Cristóvão, 2010. |
url |
https://ri.ufs.br/handle/riufs/6066 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Sergipe |
dc.publisher.program.fl_str_mv |
Pós-Graduação em Química |
dc.publisher.initials.fl_str_mv |
UFS |
dc.publisher.country.fl_str_mv |
BR |
publisher.none.fl_str_mv |
Universidade Federal de Sergipe |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFS instname:Universidade Federal de Sergipe (UFS) instacron:UFS |
instname_str |
Universidade Federal de Sergipe (UFS) |
instacron_str |
UFS |
institution |
UFS |
reponame_str |
Repositório Institucional da UFS |
collection |
Repositório Institucional da UFS |
bitstream.url.fl_str_mv |
https://ri.ufs.br/jspui/bitstream/riufs/6066/1/LUCIANO_SANTOS.pdf https://ri.ufs.br/jspui/bitstream/riufs/6066/2/LUCIANO_SANTOS.pdf.txt https://ri.ufs.br/jspui/bitstream/riufs/6066/3/LUCIANO_SANTOS.pdf.jpg |
bitstream.checksum.fl_str_mv |
cdab31def522c05f4ddbb4089d8e7bfe ed40475697ae3430e20648bda90ab702 dea554ae1291fce46c9c3f38bd2868e2 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS) |
repository.mail.fl_str_mv |
repositorio@academico.ufs.br |
_version_ |
1802110647188586496 |